Severity: Warning
Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 176
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3122
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Imatinib, a drug used for the treatment of chronic myeloid leukemia and other cancers, works by blocking the catalytic site of pathological constitutively active Abl kinase. While the binding pose is known from X-ray crystallography, the different steps leading to the formation of the complex are not well understood. The results from extensive molecular dynamics simulations show that imatinib can primarily exit the known crystallographic binding pose through the cleft of the binding site or by sliding under the αC helix. Once displaced from the crystallographic binding pose, imatinib becomes trapped in intermediate states. These intermediates are characterized by a high diversity of ligand orientations and conformations, and relaxation timescales within this region may exceed 3-4 ms. Analysis indicates that the metastable intermediate states should be spectroscopically indistinguishable from the crystallographic binding pose, in agreement with tryptophan stopped-flow fluorescence experiments.
Download full-text PDF |
Source |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288498 | PMC |
http://dx.doi.org/10.1021/acs.jctc.0c00739 | DOI Listing |
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